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Wahl, A. ; Kasela, S.* ; Monotoro, E.C.* ; van Iterson, M.* ; Štambuk, J.* ; Sharma, S. ; van den Akker, E.* ; Klaric, L.* ; Benedetti, E. ; Razdorov, G.* ; Trbojević-Akmačić, I.* ; Vučković, F.* ; Ugrina, I.* ; Beekman, M.* ; Deelen, J.* ; van Heemst, D.* ; Heijmans, B.T.* ; Benedetti, E. ; Wuhrer, M.* ; Plomp, R.* ; Keser, T.* ; Šimurina, M.* ; Pavić, T.* ; Gudelj, I.* ; Krištić, J.* ; Grallert, H. ; Kunze, S. ; Peters, A. ; Bell, J.T.* ; Spector, T.D.* ; Milani, L.* ; Eline Slagboom, P.* ; Lauc, G.* ; Gieger, C.

IgG glycosylation and DNA methylation are interconnected with smoking.

Biochim. Biophys. Acta-Gen. Subj. 1862, 637-648 (2018)
Postprint DOI PMC
Open Access Green
Background: Glycosylation is one of the most common post-translation modifications with large influences on protein structure and function. The effector function of immunoglobulin G (IgG) alters between pro- and anti-inflammatory, based on its glycosylation. IgG glycan synthesis is highly complex and dynamic. Methods: With the use of two different analytical methods for assessing IgG glycosylation, we aim to elucidate the link between DNA methylation and glycosylation of IgG by means of epigenome-wide association studies. In total, 3000 individuals from 4 cohorts were analyzed. Results: The overlap of the results from the two glycan measurement panels yielded DNA methylation of 7 CpG-sites on 5 genomic locations to be associated with IgG glycosylation: cg25189904 (chr.1, GNG12); cg05951221, cg21566642 and cg01940273 (chr.2, ALPPL2); cg05575921 (chr.5, AHRR); cg06126421 (6p21.33); and cg03636183 (chr.19, F2RL3). Mediation analyses with respect to smoking revealed that the effect of smoking on IgG glycosylation may be at least partially mediated via DNA methylation levels at these 7 CpG-sites. Conclusion: Our results suggest the presence of an indirect link between DNA methylation and IgG glycosylation that may in part capture environmental exposures. General significance: An epigenome-wide analysis conducted in four population-based cohorts revealed an association between DNA methylation and IgG glycosylation patterns. Presumably, DNA methylation mediates the effect of smoking on IgG glycosylation.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Dna Methylation ; Igg Glycosylation ; Smoking ; Ewas ; Mediation; Hydrocarbon Receptor Repressor; Epigenome-wide Association; Immunoglobulin-g; Lung-cancer; Alkaline-phosphatase; F2rl3 Methylation; N-glycosylation; Epigenetic Regulation; Ovarian-cancer; Human Placenta
Language
Publication Year 2018
Prepublished in Year 2017
HGF-reported in Year 2017
ISSN (print) / ISBN 0304-4165
e-ISSN 1872-8006
Journal Biochimica et Biophysica Acta - General Subjects
Quellenangaben Volume: 1862, Issue: 3, Pages: 637-648 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
Institute of Computational Biology (ICB)
POF-Topic(s) 30202 - Environmental Health
90000 - German Center for Diabetes Research
Research field(s) Genetics and Epidemiology
Enabling and Novel Technologies
PSP Element(s) G-504091-004
G-504000-001
G-504091-001
G-504091-002
G-501901-012
DOI 10.1016/j.bbagen.2017.10.012
WOS ID WOS:000425197300026
Scopus ID 85037988863
PubMed ID 29055820
Erfassungsdatum 2017-11-10
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